This invention relates to the preparation of 2-hydroxy-4-methylthiobutyric acid (HMBA) and more particularly to an improved process for preparing a liquid product comprising HMBA.
2-hydroxy-4-methylthiobutyric acid, commonly referred to as the hydroxy analog of methionine and also known as 2-hydroxy-4-(methylthio)butanoic acid, is an analog of the essential amino acid l-methionine. Methionine analogs such as HMBA are effective in supplying methionine for nutritional uses, particularly as a poultry feed supplement.
Commercially, HMBA has been produced as a racemic D,L-mixture by hydrolyzing 2-hydroxy-4-methylthiobutyronitrile (HMBN) with a mineral acid, precipitating the acid residue by addition of an alkaline earth hydroxide or carbonate, and recovering a salt of HMBA from the aqueous phase by evaporative crystallization. As described, for example, in Blake et al U.S. Pat. No. 2,745,745, either an ammonium salt or mixed ammonium and alkaline earth salts of the acid may be produced, depending on the molar proportions of alkaline earth hydroxide or carbonate added to the hydrolyzate to precipitate the acid residue.
Recently, processes have been developed (e.g., Cummins U.S. Pat. No. 3,773,927) for the preparation of a liquid HMBA product which comprises a high concentration, typically 85% to 90% by weight, HMBA in water. Liquid HMBA products produced in this manner exhibit a strong odor and a relatively dark color. Even when diluted 10:1 in isopropanol, the liquid product usually exhibits readings of 14 or higher on the Gardner Color Scale. Generally, the concentrated liquid product also contains ester oligomers. While most oligomers equilibrate by hydrolysis to monomeric HMBA in a system comprising .gtoreq.35% by weight water, the rate of such hydrolysis is very slow at 10% to 15% by weight water levels. This results in relatively stable oligomers which impart a relatively high viscosity to the concentrated liquid product.
Discoloration in the liquid product and oligomer formation are believed to result in significant part from exposure of HMBA to conditions of high temperature and low water content during the terminal portion of the dehydration step. Dehydration is also energy-intensive since it is necessary to remove a large proportion of water per unit weight of product. Difficulties are encountered in the filtration or centrifugation steps necessary for separation of by-product solids from the mother liquor. Yields also suffer as a result of the loss of HMBA product adhered to the surfaces of solid by-product salts removed from the process.
As an alternative to evaporative crystallization in the preparation of HMBA salts, Blake (U.S. Pat. No. 2,745,745) contains a limited disclosure of the possibility of separating the acid product from the reaction solution by extraction with a suitable water-immiscible organic liquid which is a solvent for the acid, for example, an organic liquid such as diethyl ether. In one working example, Blake describes a preparation in which HMBN was treated with concentrated hydrochloric acid, the reaction mixture cooled and ammonium chloride allowed to crystallize, the resultant slurry filtered to remove ammonium chloride, and the filtrate extracted with diethyl ether to produce an oily liquid which was treated with saturated zinc acetate solution to produce the zinc salt of HMBA.
British Patent No. 915,193 describes a process for the preparation of the calcium salt of HMBA in which HMBN is hydrolyzed to HMBA in a continuous back-mixed reactor using a dilute sulfuric acid solution, and HMBA is separated from the reaction liquor by extraction with an ether, such as isopropyl ether or butyl ether, which has a boiling point higher than ethyl ether. Water is added to the extract to form an emulsion and calcium carbonate or calcium hydroxide added to the emulsion to precipitate calcium HMBA. The British patent is not concerned with the preparation of a liquid HMBA product. Because of the use of a continuous back-mixed reaction system, the process of the British patent may not achieve complete conversion of HMBN or amide intermediate to HMBA. Although this may not present a problem in the reference process if incompletely reacted material is fully saponified under the alkaline conditions of the salt precipitation, the presence of unreacted material is undesirable where a liquid HMBA product is to be made.
Direct recovery of HMBA from the hydrolyzate by extraction is criticized in Gielkens U.S. Pat. No. 3,175,000 as providing poor yields. Gielken uses extraction for secondary recovery in a process in which HMBA is first salted out of a sulfuric acid hydrolyzate by addition of ammonium sulfate. Residual HMBA in the aqueous phase is thereafter recovered by extraction.
Cummins U.S. Pat. No. 3,773,927 describes a process in which HMBA is produced by hydrochloric acid hydrolysis of HMBN. Under the conditions described by Cummins, the hydrolysis reaction produces a slurry containing solid ammonium chloride which is removed by centrifugation. The filtrate is then vacuum distilled for separation of water. In carrying out the hydrolysis, Cummins expresses a preference for adding the HMBN to a 31% to 38% hydrochloric acid solution at 80.degree. C., after which the mass is heated to 85.degree. C. to 100.degree. C.